The interrelations between narcotic analgesic drugs and the synaptic membranes of rat brain will be investigated in three aspects: (1) the effect of acute of chronic opiate treatment on the levels or turnover rates of synaptic membranes isolated from rat brain; (2) the effect of acute or chronic opiate treatment on the activity and amount of synaptic enzymes and other unique brain proteins; and (3) the interactions between opiates and synaptic membranes including specific binding of labeled opiates and interference with neurotransmitter release from isolated nerve-endings. The effects of acute treatment of rats should be related to the initial drug: nervous tissue interactions, and the effects of chronic opiate treatment should be related to biochemical adaptation to the initial interactions. The general methodology will include the separation of the many proteins of synaptic vesicle membranes and nerve-ending membranes by gel electrophoresis and identification of proteins by molecular weight, carbohydrate or lipid content, enzyme activity, etc. The effect of opiates on neurotransmitter transport across the synaptic membrane will be examined in isolated nerve-endings from appropriate areas of rat brain. Other neurochemical techniques will be employed as needed.